Ethoxzolamide

Overview

DrugBank ID
DB00311
Type
Small Molecule
US Approved
NO
Other Approved
NO
Clinical Trials
Phase 0
0
Phase 1
0
Phase 2
0
Phase 3
0
Phase 4
0

Identification

Generic Name
Ethoxzolamide
DrugBank Accession Number
DB00311
Background

Ethoxzolamide is a sulfonamide used as diuretic and in glaucoma. It inhibits carbonic anhydrase activity in proximal renal tubules to decrease reabsorption of water, sodium, potassium, bicarbonate. Its pharmacological activity thus confers the risk for hypokalemia.

Type
Small Molecule
Groups
Withdrawn
Structure
Weight
Average: 258.317
Monoisotopic: 258.013283576
Chemical Formula
C9H10N2O3S2
Synonyms
  • 6-Ethoxy-1,3-benzothiazole-2-sulfonamide
  • Ethoxazolamide
  • Ethoxyzolamide

Pharmacology

Indication

For use in the treatment of duodenal ulcers, as a diuretic, and in the treatment of glaucoma, and may also be useful in the treatment of seizures associated with epilepsy.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Ethoxzolamide is an inhibitor of the carbonic anhydrase enzyme in proximal renal tubules that works by decreasing the reabsorption of water, sodium, potassium, bicarbonate. It also decreases the activity of carbonic anhydrase expressed in the CNS, which leads to increased seizure threshold. Inhibition of carbonic anhydrase in the eye contributes to its effect of reducing intraocular pressure and decreasing aqueous humor.

Mechanism of action

Ethoxzolamide binds to and inhibits carbonic anhydrase I, which plays an essential role in facilitating the transport of CO2 and H+ in the intracellular space, across biological membranes, and in the layers of the extracellular space. Through inhibition of the enzyme, the balance of applicable membrane equilibrium systems are affected.

TargetActionsOrganism
ACarbonic anhydrase 2
inhibitor
Humans
ACarbonic anhydrase 4
inhibitor
Humans
ACarbonic anhydrase 7
inhibitor
Humans
ACarbonic anhydrase 1
inhibitor
Humans
UCarbonic anhydrase 3
inhibitor
Humans
Absorption

Rapidly absorbed with 65% bioavailability

Volume of distribution

Not Available

Protein binding

~89%

Metabolism
Not Available
Route of elimination

Not Available

Half-life

2.5-5.5 hours

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirEthoxzolamide may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy.
AcamprosateThe excretion of Acamprosate can be decreased when combined with Ethoxzolamide.
AcarboseThe therapeutic efficacy of Acarbose can be increased when used in combination with Ethoxzolamide.
AceclofenacEthoxzolamide may increase the excretion rate of Aceclofenac which could result in a lower serum level and potentially a reduction in efficacy.
AcemetacinThe therapeutic efficacy of Ethoxzolamide can be decreased when used in combination with Acemetacin.
Food Interactions
Not Available

Products

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International/Other Brands
Cardrase (PHARMACIA AND UPJOHN) / Ethamide (ALLERGAN)

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzothiazoles. These are organic compounds containing a benzene fused to a thiazole ring (a five-membered ring with four carbon atoms, one nitrogen atom and one sulfur atom).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiazoles
Sub Class
Not Available
Direct Parent
Benzothiazoles
Alternative Parents
Alkyl aryl ethers / Organosulfonamides / Benzenoids / Thiazoles / Heteroaromatic compounds / Aminosulfonyl compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides
show 1 more
Substituents
1,3-benzothiazole / Alkyl aryl ether / Aminosulfonyl compound / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid / Ether / Heteroaromatic compound / Hydrocarbon derivative
show 12 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzothiazoles, sulfonamide (CHEBI:101096)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
Z52H4811WX
CAS number
452-35-7
InChI Key
OUZWUKMCLIBBOG-UHFFFAOYSA-N
InChI
InChI=1S/C9H10N2O3S2/c1-2-14-6-3-4-7-8(5-6)15-9(11-7)16(10,12)13/h3-5H,2H2,1H3,(H2,10,12,13)
IUPAC Name
6-ethoxy-1,3-benzothiazole-2-sulfonamide
SMILES
CCOC1=CC2=C(C=C1)N=C(S2)S(N)(=O)=O

References

Synthesis Reference

Korman, J.; U.S. Patent 2,868,800; January 13, 1959; assigned to The Upjohn Company.

General References
Not Available
Human Metabolome Database
HMDB0014456
KEGG Drug
D02441
PubChem Compound
3295
PubChem Substance
46509023
ChemSpider
3179
BindingDB
10882
ChEBI
101096
ChEMBL
CHEMBL18
ZINC
ZINC000000056721
Therapeutic Targets Database
DAP000598
PharmGKB
PA164754743
PDBe Ligand
EZL
Wikipedia
Ethoxzolamide
PDB Entries
3caj / 3dcw / 3dd0 / 3mdz / 5jn9 / 5tt3 / 6bcc / 6mwi / 6ql2

Clinical Trials

Clinical Trials
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PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns

Pharmacoeconomics

Manufacturers
  • Pharmacia and upjohn co
  • Allergan pharmaceutical
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)188-190.5Korman, J.; U.S. Patent 2,868,800; January 13, 1959; assigned to The Upjohn Company.
water solubility40 mg/LYALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.01HANSCH,C ET AL. (1995)
logS-3.81ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.688 mg/mLALOGPS
logP1.87ALOGPS
logP1.6Chemaxon
logS-2.6ALOGPS
pKa (Strongest Acidic)7.51Chemaxon
pKa (Strongest Basic)-1.9Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area82.28 Å2Chemaxon
Rotatable Bond Count3Chemaxon
Refractivity59.97 m3·mol-1Chemaxon
Polarizability25.27 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.8667
Caco-2 permeable-0.6038
P-glycoprotein substrateNon-substrate0.6875
P-glycoprotein inhibitor INon-inhibitor0.8793
P-glycoprotein inhibitor IINon-inhibitor0.9528
Renal organic cation transporterNon-inhibitor0.8576
CYP450 2C9 substrateNon-substrate0.8346
CYP450 2D6 substrateNon-substrate0.7982
CYP450 3A4 substrateNon-substrate0.6017
CYP450 1A2 substrateInhibitor0.6223
CYP450 2C9 inhibitorInhibitor0.62
CYP450 2D6 inhibitorNon-inhibitor0.8842
CYP450 2C19 inhibitorInhibitor0.6582
CYP450 3A4 inhibitorNon-inhibitor0.6471
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5599
Ames testNon AMES toxic0.5832
CarcinogenicityNon-carcinogens0.7065
BiodegradationNot ready biodegradable0.9846
Rat acute toxicity2.5056 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9429
hERG inhibition (predictor II)Non-inhibitor0.8419
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (10.1 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0fb9-1980000000-ec067e5e789b4033729a
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0uk9-3900000000-26213ae94b481c876007
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0uk9-3900000000-26213ae94b481c876007
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0090000000-7587f29079fe256c8a10
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9000000000-7750f0147ae8ae1dd964
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-01t9-9000000000-a40fa9445d0cd1011ea9
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0090000000-e522e661917ae594ded3
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9610000000-d603ee8838b870bb2c31
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-08i0-0940000000-4667d85f09051e0d471f
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-162.4085459
predicted
DarkChem Lite v0.1.0
[M-H]-162.8913459
predicted
DarkChem Lite v0.1.0
[M-H]-151.90479
predicted
DeepCCS 1.0 (2019)
[M+H]+162.8070459
predicted
DarkChem Lite v0.1.0
[M+H]+163.2533459
predicted
DarkChem Lite v0.1.0
[M+H]+154.2628
predicted
DeepCCS 1.0 (2019)
[M+Na]+162.9455459
predicted
DarkChem Lite v0.1.0
[M+Na]+163.0169459
predicted
DarkChem Lite v0.1.0
[M+Na]+160.35606
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Details
1. Carbonic anhydrase 2
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Catalyzes the reversible hydration of carbon dioxide (PubMed:11327835, PubMed:11802772, PubMed:11831900, PubMed:12056894, PubMed:12171926, PubMed:1336460, PubMed:14736236, PubMed:15300855, PubMed:15453828, PubMed:15667203, PubMed:15865431, PubMed:16106378, PubMed:16214338, PubMed:16290146, PubMed:16686544, PubMed:16759856, PubMed:16807956, PubMed:17127057, PubMed:17251017, PubMed:17314045, PubMed:17330962, PubMed:17346964, PubMed:17540563, PubMed:17588751, PubMed:17705204, PubMed:18024029, PubMed:18162396, PubMed:18266323, PubMed:18374572, PubMed:18481843, PubMed:18618712, PubMed:18640037, PubMed:18942852, PubMed:1909891, PubMed:1910042, PubMed:19170619, PubMed:19186056, PubMed:19206230, PubMed:19520834, PubMed:19778001, PubMed:7761440, PubMed:7901850, PubMed:8218160, PubMed:8262987, PubMed:8399159, PubMed:8451242, PubMed:8485129, PubMed:8639494, PubMed:9265618, PubMed:9398308). Can also hydrate cyanamide to urea (PubMed:10550681, PubMed:11015219). Stimulates the chloride-bicarbonate exchange activity of SLC26A6 (PubMed:15990874). Essential for bone resorption and osteoclast differentiation (PubMed:15300855). Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption
Specific Function
arylesterase activity
Gene Name
CA2
Uniprot ID
P00918
Uniprot Name
Carbonic anhydrase 2
Molecular Weight
29245.895 Da
References
  1. Mincione F, Scozzafava A, Supuran CT: The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents. Curr Pharm Des. 2008;14(7):649-54. [Article]
  2. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Details
2. Carbonic anhydrase 4
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Catalyzes the reversible hydration of carbon dioxide into bicarbonate and protons and thus is essential to maintaining intracellular and extracellular pH (PubMed:15563508, PubMed:16686544, PubMed:16807956, PubMed:17127057, PubMed:17314045, PubMed:17652713, PubMed:17705204, PubMed:18618712, PubMed:19186056, PubMed:19206230, PubMed:7625839). May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis (PubMed:15563508). It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid (PubMed:15563508)
Specific Function
carbonate dehydratase activity
Gene Name
CA4
Uniprot ID
P22748
Uniprot Name
Carbonic anhydrase 4
Molecular Weight
35032.075 Da
References
  1. Mincione F, Scozzafava A, Supuran CT: The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents. Curr Pharm Des. 2008;14(7):649-54. [Article]
Details
3. Carbonic anhydrase 7
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Reversible hydration of carbon dioxide
Specific Function
carbonate dehydratase activity
Gene Name
CA7
Uniprot ID
P43166
Uniprot Name
Carbonic anhydrase 7
Molecular Weight
29658.235 Da
References
  1. Mincione F, Scozzafava A, Supuran CT: The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents. Curr Pharm Des. 2008;14(7):649-54. [Article]
Details
4. Carbonic anhydrase 1
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Catalyzes the reversible hydration of carbon dioxide (PubMed:10550681, PubMed:16506782, PubMed:16686544, PubMed:16807956, PubMed:17127057, PubMed:17314045, PubMed:17407288, PubMed:18618712, PubMed:19186056, PubMed:19206230). Can hydrate cyanamide to urea (PubMed:10550681)
Specific Function
arylesterase activity
Gene Name
CA1
Uniprot ID
P00915
Uniprot Name
Carbonic anhydrase 1
Molecular Weight
28870.0 Da
References
  1. Kohling R, Vreugdenhil M, Bracci E, Jefferys JG: Ictal epileptiform activity is facilitated by hippocampal GABAA receptor-mediated oscillations. J Neurosci. 2000 Sep 15;20(18):6820-9. [Article]
  2. Perez Velazquez JL: Bicarbonate-dependent depolarizing potentials in pyramidal cells and interneurons during epileptiform activity. Eur J Neurosci. 2003 Sep;18(5):1337-42. [Article]
  3. Heck RW, Tanhauser SM, Manda R, Tu C, Laipis PJ, Silverman DN: Catalytic properties of mouse carbonic anhydrase V. J Biol Chem. 1994 Oct 7;269(40):24742-6. [Article]
  4. Siffert W, Gros G: Carbonic anhydrase C in white-skeletal-muscle tissue. Biochem J. 1982 Sep 1;205(3):559-66. [Article]
  5. Scozzafava A, Briganti F, Ilies MA, Supuran CT: Carbonic anhydrase inhibitors: synthesis of membrane-impermeant low molecular weight sulfonamides possessing in vivo selectivity for the membrane-bound versus cytosolic isozymes. J Med Chem. 2000 Jan 27;43(2):292-300. [Article]
  6. Bertucci A, Innocenti A, Zoccola D, Scozzafava A, Tambutte S, Supuran CT: Carbonic anhydrase inhibitors. Inhibition studies of a coral secretory isoform by sulfonamides. Bioorg Med Chem. 2009 Jul 15;17(14):5054-8. doi: 10.1016/j.bmc.2009.05.063. Epub 2009 May 30. [Article]
Details
5. Carbonic anhydrase 3
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Reversible hydration of carbon dioxide
Specific Function
carbonate dehydratase activity
Gene Name
CA3
Uniprot ID
P07451
Uniprot Name
Carbonic anhydrase 3
Molecular Weight
29557.215 Da
References
  1. Nishimori I, Minakuchi T, Onishi S, Vullo D, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Bioorg Med Chem. 2007 Dec 1;15(23):7229-36. Epub 2007 Aug 25. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)
Specific Function
alpha-ketoglutarate transmembrane transporter activity
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Uwai Y, Saito H, Hashimoto Y, Inui KI: Interaction and transport of thiazide diuretics, loop diuretics, and acetazolamide via rat renal organic anion transporter rOAT1. J Pharmacol Exp Ther. 2000 Oct;295(1):261-5. [Article]

Drug created at June 13, 2005 13:24 / Updated at November 09, 2024 05:52